The proposed Program Project is the second renewal of a collaborative effort of long-standing colleagues in order to apply the most modern methods of cellular, subcellular and molecular physiology, cell biology and biochemistry to respiratory function, particularly tissue 02 and C02 and its maintenance by the ventilatory function of the lung. Two projects involve studies on tissue P02; the mechanism of sensing arterial P02 (and PC02) by the peripheral chemoreceptors, and the tension responses to changing P02 of vascular smooth muscle. One project involves studies on PC02 in tissues; the measurement of the kinetics of C02 movements in lung, blood and muscular tissues and in subcellular particles, mitochondria and sarcoplasmic reticulum. Three projects involve pulmonary cellular physiology; a duo concern lung surfactant, the mechanisms of regulation of its synthesis, the regulation of its secretion and its recycling and a final project concerns phosphoinositide transduction in airway smooth muscle. An instrumention core, supplies analytical and consultative services for the different projects and includes two mass spectrometers for analysis of stable isotopes in labelled compounds, and biophysical analytical instruments, among which are split beam spectrophotometers for intracellular measurements in tissues and cell suspensions. A cell Morphology Core will provide consultative collaboration in electron microscopy which is essential to the majority of the projects. The investigators are all members of the Respiratory Group of the Department of Physiology and are closely related to other groups engaged in research in respiration at the University of Pennsylvania. The results should contribute to our understanding of the movements and transport of 02 and C02 in the periphery, to the metabolism of lung phospholipids and the control of airway tone.